FLUCONAZOLE

Posology The dose should be based on the nature and severity of the fungal infection. The treatment of infections requiring multiple dosing should be continued until clinical parameters or laboratory results show that the active fungal infection has subsided.

An inadequate period of treatment may lead to recurrence of the active infection.

Adults:

Indications Posology Duration of treatment - Treatment of cryptococcal meningitis Loading dose: 400 mg on Day 1 Subsequent dose: 200 mg to 400 mg once daily Usually at least 6 to 8 weeks. In life threatening infections the daily dose can be increased to 800 mg Cryptococcosis - Maintenance therapy to prevent relapse of cryptococcal 200 mg once daily Indefinitely at a daily dose of 200 mg meningitis in patients with high risk of recurrence Coccidioidomycosis 200 mg to 400 mg once daily 11 months up to 24 months or longer depending on the patient.

800 mg daily may be considered for some infections and especially for meningeal disease Invasive candidiasis Loading dose: 800 mg on Day 1 Subsequent dose: 400 mg once daily In general, the recommended duration of therapy for candidemia is for 2 weeks after first negative blood culture result and resolution of signs and symptoms attributable to candidemia Oropharyngeal candidiasis Loading dose: 200 mg to 400 mg on Day 1 Subsequent dose: 100 mg to 200 mg once daily 7 to 21 days (until oropharyngeal candidiasis is in remission).

Longer periods may be used in patients with severely compromised immune function Oesophageal candidiasis Loading dose: 200 mg to 400 mg on Day 1 Subsequent dose: 100 mg to 200 mg once daily 14 to 30 days (until oesophageal candidiasis is in remission).

Longer periods may be used in patients with severely compromised immune function Candiduria 200 mg to 400 mg once daily 7 to 21 days. Longer periods may be used in patients with severely compromised immune function. Chronic atrophic candidiasis 50 mg once daily 14 days Treatment of mucosal candidiasis Chronic mucocutaneous candidiasis 50 mg to 100 mg once daily Up to 28 days.

Longer periods depending on both the severity of infection or underlying immune compromisation and infection Oropharyngeal candidiasis 100 mg to 200 mg once daily or 200 mg daily or 200 mg 3 times per week An indefinite period for patients with chronic immune suppression Prevention of relapse of mucosal candidiasis in patients infected with HIV who are at high risk of experiencing relapse Oesophageal candidiasis 100 mg to 200 mg once daily or 200 mg 3 times per week An indefinite period for patients with chronic immune suppression Prophylaxis of candidal infections in patients with prolonged neutropenia 200 mg to 400 mg once daily Treatment should start several days before the anticipated onset of neutropenia and continue for 7 days after recovery from neutropenia after the neutrophil count rises above 1 000 cells per mm3.

4). The most frequently (>1/10) reported adverse reactions are headache, abdominal pain, diarrhoea, nausea, vomiting, alanine aminotransferase increased, aspartate aminotransferase increased, blood alkaline phosphatase increased and rash.

The following adverse reactions have been observed and reported during treatment with fluconazole with the following frequencies: Very common (≥1/10); Common (≥1/100 to <1/10) Uncommon (≥1/1,000 to <1/100) Rare (≥1/10,000 to <1/1,000) Very rare (<1/10,000) Not known (cannot be estimated from the available data).

4), exfoliative dermatitis, angioedema, face oedema, alopecia Drug reaction with eosinophilia and systemic symptoms (DRESS) Musculoskeletal and connective tissue disorders Myalgia General disorders and administration site conditions Fatigue, malaise, asthenia, fever *including Fixed Drug Eruption Paediatric population The pattern and incidence of adverse reactions and laboratory abnormalities recorded during paediatric clinical trials are comparable to those seen in adults.

Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

Tinea capitis Fluconazole has been studied for treatment of tinea capitis in children. It was shown not to be superior to griseofulvin and the overall success rate was less than 20%. Therefore, Fluconazole should not be used for tinea capitis.

g. pulmonary and cutaneous cryptococcosis) is limited, which prevents dosing recommendations. Deep endemic mycoses The evidence for efficacy of fluconazole in the treatment of other forms of endemic mycoses such as paracoccidioidomycosis, lymphocutaneous sporotrichosis and histoplasmosis is limited, which prevents specific dosing recommendations.

2). Adrenal insufficiency Ketoconazole is known to cause adrenal insufficiency, and this could also, although rarely seen, be applicable to fluconazole. 5, ‘The effects of fluconazole on other medicinal products’. Hepatobiliary system Fluconazole should be administered with caution to patients with liver dysfunction.

Fluconazole has been associated with rare cases of serious hepatic toxicity including fatalities, primarily in patients with serious underlying medical conditions. In cases of fluconazole associated hepatotoxicity, no obvious relationship to total daily dose, duration of therapy, sex or age of patient has been observed.

Fluconazole hepatotoxicity has usually been reversible on discontinuation of therapy. Patients who develop abnormal liver function tests during fluconazole therapy must be monitored closely for the development of more serious hepatic injury.

The patient should be informed of suggestive symptoms of serious hepatic effects (important asthenia, anorexia, persistent nausea, vomiting and jaundice). Treatment with fluconazole should be immediately discontinued and the patient should consult a physician.

Cardiovascular system Some azoles, including fluconazole, have been associated with prolongation of the QT-interval on the electrocardiogram. Fluconazole causes QT prolongation via the inhibition of Rectifier Potassium Channel current (Ikr).

1. Co-administration of terfenadine is contraindicated in patients receiving Fluconazole at multiple doses of 400 mg per day or higher based upon results of a multiple dose interaction study. 5).